Pharmacokinetics in children

The studies by Chien et al. show that the clearance (l/hour/kg) of levofloxacin increases as the bodyweight increases.

In addition, the following kinetic parameters have been found, after a single dose of 7 mg/kg (max 500 mg/dose) [Chien]

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Renal impaiment in children > 3 months

Oral
GFR 50-80 ml/min/1.73m²: Adjustment is not required
GFR 30-50 ml/min/1.73m²: 100% of the normal dose each time and the interval between two doses: 24 hours
GFR 10-30 ml/min/1.73m²: 50% of the normal dose each time and the interval between two doses: 24 hours.
GFR < 10 ml/min/1.73m²:      Generalized recommendations cannot be given.

IV
GFR 50-80 ml/min/1.73m²: Adjustment is not required
GFR 30-50 ml/min/1.73m²:
100% of the normal dose each time and interval between two doses: 48 hours
OR
50% of the normal dose each time and the interval between two doses: 24 hours
GFR 10-30 ml/min/1.73m²:
50% of the normal dose each time and interval between two doses: 48 hours
OR
25% of the normal dose each time and the interval between two doses: 24 hours
GFR < 10 ml/min/1.73m²: Generalized recommendations cannot be given.

Clinical consequences

Neurological side-effects of quinolones are headaches, dizziness, drowsiness, paraesthesia, peripheral neuropathy, peripheral sensory impairment, vision disorders and confusion. These complaints are usually reversible and dose-dependent. There have been rare reports of convulsions, particularly in patients with a previous history of epilepsy or cerebrovascular insufficiency.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Nausea, diarrhoea, vomiting, abdominal pain, headaches, dizziness, allergic skin reaction, increased liver enzyme values, abnormal blood counts, convulsions and myalgia. Further: arthralgia, tendinopathy, arthritis and abnormal gait. These musculoskeletal side effects are reversible by nature as well as occurring more often in children who have been treated with levofloxacin than in children who have been treated with another antibiotic [Noel et al.].
Animal tests have shown that the use of fluoroquinolones in young test animals causes abnormalities in cartilage formation. These deviations were not demonstrated in the study that was carried out in young children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Caution is needed when giving quinolones to children in the growth phase. Its use should be restricted to cases in which there are no other therapeutic options.

In experimental animal research, arthropathy was observed to a varying extent when very high doses were given to young dogs. These side effects have never been reported in humans either: fluoroquinolones are therefore being used to an increasing extent in children if there are no other therapeutic possibilities or if there are serious objections against the use of other broad-spectrum antibiotics.

Fluoroquinolones are ‘reserve’ antimicrobial agents. To prevent the development of resistance, its use should be reserved for situations in which other antimicrobial drugs give insufficient results.
Caution is needed in children with a tendency to convulsions and in children with a known risk of lengthening of the QT interval.

The use of fluoroquinolones (by mouth, lungs (inhalation) and injections) increases the risk of long-term and possibly permanent damage to the muscles and nervous system. Caution is needed when prescribing fluoroquinolones in patients with renal impairment, patients with solid organ transplants and patients on concomitant corticosteroid therapy. The risk of fluoroquinolone-induced tendonitis and tendon rupture may be increased in these patients.(DHPC)

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• ANTIINFECTIVES FOR SYSTEMIC USE
• ANTIBACTERIALS FOR SYSTEMIC USE

QUINOLONE ANTIBACTERIALS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

References

1. Danisovicová A, et al, Magnetic resonance imaging in children receiving quinolones: no evidence of quinolone-induced arthropathy. A multicenter survey, Chemotherapy, 1994, 40, 209-14
2. Arguedas A, et al, An open-label, double tympanocentesis study of levofloxacin therapy in children with, or at high risk for, recurrent or persistent acute otitis media, Pediatr Infect Dis J, 2006, 25, 1102-9
3. Bethell DB, et al, Effects on growth of single short courses of fluoroquinolones., Arch Dis Child, 1996, 74, 44-6
4. Bradley JS, et al, Comparative study of levofloxacin in the treatment of children with community-acquired pneumonia, Pediatr Infect Dis J, 2007, 26, 868-78
5. Chien S, et al, Levofloxacin pharmacokinetics in children, J Clin Pharmacol., 2005, 45, 153-60
6. Noel GJ, et al, A randomized comparative study of levofloxacin versus amoxicillin/clavulanate for treatment of infants and young children with recurrent or persistent acute otitis media., Pediatr Infect Dis J., 2008, 27, 483-9
7. Noel GJ, et al, Comparative safety profile of levofloxacin in 2523 children with a focus on four specific musculoskeletal disorders, Pediatr Infect Dis J., 2007, 26, 879-91
8. Schaad UB, et al, Use of fluoroquinolones in pediatrics: consensus report of an International Society of Chemotherapy commission., Pediatr Infect Dis J, 1995, 14, 1-9
9. Hartwig NC, et al, Vademecum pediatrische antimicrobiele therapie, 2005
10. Bradley JS et al. , Assessment of musculoskeletal toxicity 5 years after therapy with levofloxacin., Pediatrics. , 2014, Jul;134(1), e146-53
11. Sanofi-Aventis, SmPC Tavanic tablet (RVG 21811,21812) 15-07-2013, www.geneesmiddeleninformatiebank.nl
12. Bayer Int, DHPC Fluorochinolonen, 29 maart 2019
13. BfArM., Rote-Hand-Brief zu Fluorchinolon-Antibiotika. 08.04.2019. https://www.bfarm.de/SharedDocs/Risikoinformationen/Pharmakovigilanz/DE/RHB/2019/rhb-fluorchinolone.pdf;jsessionid=4D7FF38A3DCDA1F9795930B56FD1B5E8.2_cid329?__blob=publicationFile&v=3, zuletzt aufgerufen am 12.04.2019.
14. 1A Pharma, SmPC Levofloxacin - 1 A Pharma® Filmtabletten (70347.00.00/ 70348.00.00), 07/2015
15. European Committee on Antimicrobial Susceptibility Testing - EUCAST, Clinical breakpoints - breakpoints and guidance, https://www.eucast.org/clinical_breakpoints, Jan 2, 2023
16. Dutch Working Party on Antibiotic Policy (SWAB) - Special Interest Group Pediatrics, Expert opinion on high dosing for infections caused by microorganisms susceptible to increased doses., Dec 6, 2022
17. Heads of Medicines Agencies (EMA -HMA), Rapporteur’s Public Paediatric Assessment Report for paediatric studies submitted in accordance with Article 45 of Regulation (EC) No1901/2006, as amended- Levofloxacin, https://www.hma.eu/fileadmin/dateien/Human_Medicines/CMD_h_/Paediatric_Regulation/Assessment_Reports/Article_45_work-sharing/Levofloxacin_2010_11_45_PdAR.pdf

Changes

Therapeutic Drug Monitoring

Overdose